Exon scrambling of MLL transcripts occur commonly and mimic partial genomic duplication of the gene

Caldas, Carlos; So, Chi Wai Eric; MacGregor, Angus; Ford, Anthony M.; McDonald, Bernadette; Li, Chan; Wiedemann, Leanne M.

doi:10.1016/s0378-1119(97)00640-9

Cited by 73 publications

(62 citation statements)

References 31 publications

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“…A method to systematically screen for MLL partner genes may become increasingly important for patient stratification (as demonstrated in childhood and adult MLL-AF9 positive AML 29,37,38 ), and all karyotype positive patients for MLL gene rearrangement may be screened 9,39 to identify partner genes and breakpoint location. This type of molecular information may be pivotal during patient follow-up to facilitate monitoring of minimal residual disease by RQ-PCR (ie with TaqMan s technology using patient-specific plasmid standards, and the MLL universal forward primer and probe combined to a partner specific reverse primer 33 ). Recent work report that chromosomal translocations and their FG transcripts may be important molecular markers for leukemia and lymphoma subtyping and disease stratification.…”

Section: Resultsmentioning

confidence: 99%

“…Previous studies show that splicing of MLL is extremely complex, and several abnormally spliced MLL transcripts have been described in both malignant and normal tissues. 33,34 In these mis-spliced products, MLL exons are joined in aberrant genomic orientation (exon scrambling) and are not the result of exon duplication. For example, we observed DUP positive spots in several cases in addition to positive spots for another partner gene for the same patient sample.…”

Section: Mll Internal Tandem Duplications (Mll-dup)mentioning

confidence: 99%

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A diagnostic biochip for the comprehensive analysis of MLL translocations in acute leukemia

Maroc¹,

Morel²,

Beillard

et al. 2004

Leukemia

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Section: Resultsmentioning

confidence: 99%

Section: Mll Internal Tandem Duplications (Mll-dup)mentioning

confidence: 99%

A diagnostic biochip for the comprehensive analysis of MLL translocations in acute leukemia

Maroc¹,

Morel²,

Beillard

et al. 2004

Leukemia

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“…This demonstrated an inframe fusion of exons 2 and 6 suggesting that a PTD event had taken place. Recent reports have confirmed that PTD fusion transcripts are detectable in normal (non-leukaemic) cells 17 and may represent a normal post-transcriptional 'exon scrambling' phenomenon, 18 thus precluding the use of nested RT-PCR alone as a means for detection of PTDs. Confirmation using genomic PCR or Southern blot analysis is recommended where possible.…”

Section: Discussionmentioning

confidence: 99%

MLL amplification in acute leukaemia: a United Kingdom Cancer Cytogenetics Group (UKCCG) study

et al. 2000

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The MLL gene, located at 11q23, is frequently rearranged in acute leukaemia as either chimaeric fusion genes or partial tandem duplications. We report a series of 12 acute leukaemia cases with apparent amplification of the MLL gene ascertained using fluorescence in situ hybridisation (FISH). Seven cases showed intrachromosomal amplification of MLL, four cases showed extrachromosomal amplification as double minute chromosomes (dmin) and one case had separate subclones with dmin and homogenously staining region (hsr). Southern blot analysis of the MLL gene showed MLL gene rearrangement in three of the 10 successful cases. These cases do not naturally fall into either of the two recognised categories of MLL rearrangement and may represent a third variety of MLL gene abnormalities.

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“…A complex pattern of alternative splicing with exon scrambling has been reported for the MLL gene in both normal and malignant cells. [40][41][42] Alternative splicing and cryptic splice site activation during RNA processing of MLL-AF4 chimeric transcripts has been observed. 43 Recently, splice variants for MLL-MLLT10 fusion transcripts were also reported by Angioni et al 11 Clearly, alternative splicing of the normal MLL gene may result in increased complexity of the biological function of MLL and possibly the same holds for the splice variants of the hybrid transcripts.…”

Section: Figurementioning

confidence: 99%

Molecular cytogenetic analysis of 10;11 rearrangements in acute myeloid leukemia

et al. 2002

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MLLT10(previously called AF10) is a moderately common MLL fusion partner predominantly occurring in acute monoblastic leukemia (AML-M5). 10;11 rearrangements require at least three breaks in order to generate an in-frame MLL-MLLT10 fusion as a result of the opposite orientations of both genes on the respective chromosome arms. In this study, we describe a detailed molecular cytogenetic analysis of MLL-MLLT10 positive 10;11 rearrangements in two patients. We observed an as yet unreported chromosomal mechanism with at least four breakpoints, leading to MLL-MLLT10 gene fusion in a 24-yearold male. An inversion of 11q13-q23 with a breakpoint in the MLL gene was followed by an additional break 3′ of MLL prior to insertion of the 11q segment into MLLT10. In a second patient, a 37-year-old male with AML-M5b, molecular cytogenetic analysis of an apparent 10;11 reciprocal translocation showed an intrachromosomal inversion of 3′MLLT10 followed by a reciprocal translocation between 10p12 and 11q23. Review of the literature showed that all cases were the result of an inversion of either 10p or 11q followed by translocation 10p;11q or insertion of the inverted segment into MLLT10 or MLL.

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Exon scrambling of MLL transcripts occur commonly and mimic partial genomic duplication of the gene

Cited by 73 publications

References 31 publications

A diagnostic biochip for the comprehensive analysis of MLL translocations in acute leukemia

A diagnostic biochip for the comprehensive analysis of MLL translocations in acute leukemia

MLL amplification in acute leukaemia: a United Kingdom Cancer Cytogenetics Group (UKCCG) study

Molecular cytogenetic analysis of 10;11 rearrangements in acute myeloid leukemia

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